Percutaneous Direct Needle Puncture and Transcatheter N-butyl Cyanoacrylate Injection Techniques for the Embolization of Pseudoaneurysms and Aneurysms of Arteries Supplying the Hepato-pancreato-biliary System and Gastrointestinal Tract.

AIMS: The aim of this study was to evaluate the safety and clinical efficacy of percutaneous direct needle puncture and transcatheter N-butyl cyanoacrylate (NBCA) injection techniques for the embolization of pseudoaneurysms and aneurysms of arteries supplying the hepato-pancreato-biliary (HPB) system and gastrointestinal (GI) tract. SUBJECTS AND METHODS: A hospital-based cross-sectional retrospective study was conducted, where the study group comprised 11 patients with pseudoaneurysms/aneurysms of arteries supplying the HPB system and GI tract presenting to a tertiary care center from January 2015 to June 2016. Four patients (36.4%) underwent percutaneous direct needle puncture of pseudoaneurysms with NBCA injection, 3 patients (27.3%) underwent transcatheter embolization with NBCA as sole embolic agent, and in 4 patients (36.4%), transcatheter NBCA injection was done along with coil embolization. RESULTS: This retrospective study comprised 11 patients (8 males and 3 females) with mean age of 35.8 years ± 1.6 (standard deviation [SD]). The mean volume of NBCA: ethiodized oil (lipiodol) mixture injected by percutaneous direct needle puncture was 0.62 ml ± 0.25 (SD) (range = 0.5-1 ml), and by transcatheter injection, it was 0.62 ml ± 0.37 (SD) (range = 0.3-1.4 ml). Embolization with NBCA was technically and clinically successful in all patients (100%). No recurrence of bleeding or recurrence of pseudoaneurysm/aneurysm was noted in our study. CONCLUSIONS: Percutaneous direct needle puncture of visceral artery pseudoaneurysms and NBCA glue injection and transcatheter NBCA injection for embolization of visceral artery pseudoaneurysms and aneurysms are cost-effective techniques that can be used when coil embolization is not feasible or has failed.

Historical epidemiology of hepatitis C virus (HCV) in select countries - volume 2.

Chronic hepatitis C virus (HCV) infection is a leading cause of liver related morbidity and mortality. In many countries, there is a lack of comprehensive epidemiological data that are crucial in implementing disease control measures as new treatment options become available. Published literature, unpublished data and expert consensus were used to determine key parameters, including prevalence, viremia, genotype and the number of patients diagnosed and treated. In this study of 15 countries, viremic prevalence ranged from 0.13% in the Netherlands to 2.91% in Russia. The largest viremic populations were in India (8 666 000 cases) and Russia (4 162 000 cases). In most countries, males had a higher rate of infections, likely due to higher rates of injection drug use (IDU). Estimates characterizing the infected population are critical to focus screening and treatment efforts as new therapeutic options become available.

Association of interleukin-10 polymorphisms with chronic hepatitis C virus infection in a case-control study and its effect on the response to combined pegylated interferon/ribavirin therapy.

We conducted a case-control study involving 150 genotype 3 chronic hepatitis C virus (HCV) patients and 150 healthy controls to investigate the association of polymorphisms in the interleukin-10 (IL-10) gene with chronic HCV infection and the association of these polymorphic variants with the combination of pegylated interferon (Peg-IFN) and ribavirin therapy response. Our data revealed that the GG genotype of IL-10 -1082A/G exhibited significant association with genotype 3 chronic HCV infection compared to controls. Treatment response data also showed a significant increase in risk for the GG genotype of IL-10 -1082A/G in response-relapse patients or non-responder patients compared to sustained virological response patients. Further, a significant increase in risk was also revealed for the CC genotype of IL-10 -592A/C in response-relapse patients or non-responder patients compared to sustained virological response patients, suggesting a role of the GG genotype of IL-10 -1082A/G and CC genotype of IL-10 -592A/C in the treatment outcome of combined Peg-IFN/ribavirin therapy.

Brain MR imaging and 1H-MR spectroscopy changes in patients with extrahepatic portal vein obstruction from early childhood to adulthood.

BACKGROUND AND PURPOSE: MR imaging and (1)H-MR spectroscopy changes are well reported in cirrhotic patients, whereas they are inadequately reported in EHPVO. The aim of this study was to investigate age-related changes in brain MR imaging and metabolite profile in EHPVO with and without MHE and to explore any correlation of imaging and (1)H-MR spectroscopy parameters with blood ammonia. MATERIALS AND METHODS: Sixty-three patients with EHPVO (children, 7-12 years [n = 22], adolescents, 13-18 years [n = 15] and adults, 19-41 years [n = 26]) and 47 healthy age/sex-matched volunteers were studied. Neuropsychological tests, MR imaging, (1)H-MR spectroscopy, and blood ammonia estimation were performed in all subjects. RESULTS: Of 63 EHPVO patients, 25 (40%) who had MHE showed significantly increased MD, Glx, and blood ammonia in all 3 age groups; however, myo-inositol was significantly lower only in adults when compared with controls. MD positively correlated with blood ammonia and Glx in all age groups. Brain choline levels were normal in all patients with different age groups. CONCLUSIONS: Increases in brain MD, Glx, and blood ammonia were associated with MHE in all age groups. Normal brain choline in EHPVO signifies healthy liver and may serve as a diagnostic marker for its differentiation from cirrhosis-induced encephalopathy. Significant decrease of myo-inositol in adults is probably due to cellular osmoregulation secondary to long-standing hyperammonemia.

Injury patterns in low intensity conflict.

SUMMARY: Injury patterns and their outcome has been the subject of interest in all kinds of military conflicts. This retrospective study was conducted in a tertiary care hospital (Level I trauma centre) to find out the trends in injuries in low intensity conflict, adequacy of pre hospital treatment, mortality patterns and adequacy of treatment after reaching tertiary care hospital. 418 patients were treated over a period of two years. All were male and 76% younger than 30 years of age. 61% patients reported directly from the site of incident and 39% were transferred from other trauma centre. Two-third of patients (73.9%) reported with at least one limb injury and 44.9% with extremity injury alone. Multiple injuries were most common injury (29%). Head and neck injuries were seen in 20% patients and Thoracic and abdominal injuries were seen in 2.6% and 3.4% patients only. Most common mode of injury was Gunshot wound (41.4%), followed by splinter injuries (39.2%) and Road traffic accident(RTA) (19.4%). Overall mortality was 3.8% and inpatient mortality of 1.4%. Head and neck injuries were leading cause of death followed by thoracic injuries.

QSAR analysis of indazole estrogens as selective beta-estrogen receptor ligands: rationalization of physicochemical properties.

Quantification of structure activity relationships was performed on a series of indazole estrogen analogs, for their relative beta estrogenic receptor agonist activity, in order to understand the essential structural requirements for selectivity of indazole estrogen analogs for beta-estrogenic receptor over alpha-estrogenic receptor. The de novo and Hansch approach suggested that the 3(rd) position of indazole nucleus (R(1)) is decisive for the selectivity of molecules towards beta-estrogenic receptor over alpha-estrogenic receptor. The study also depicted that the substitution of polar group at R(1) position might prove helpful in the beta-estrogenic receptor selectivity (ER(beta/alpha )).

Inflation with air via a facepiece for facilitating insertion of a nasogastric tube: a prospective, randomised, double-blind study.

Insertion of a nasogastric tube is a routine procedure but during anaesthesia it is often difficult and time consuming. One hundred and sixty adults undergoing elective surgery under general anaesthesia were randomly divided into two groups. After induction of anaesthesia, neuromuscular blockade and tracheal intubation, a nasogastric tube was inserted through the nose with the head of the patient in the neutral position, either with or without prior inflation with air via a facepiece attached to a self-inflating bag applied firmly with the face. Insertion of the nasogastric tube was successful in 75/78 (96%) following inflation compared with 54/80 (68%) without inflation (p<0.001). In four patients receiving inflation, a fibreoptic endoscope was passed as far as the upper oesophageal sphincter; this revealed opening of the upper oesophageal sphincter during inflation.

Gastroduodenal dysmotility in patients with gallbladder carcinoma: frequency of occurrence and clinical importance.

BACKGROUND: Gastric stasis, common in patients with gall-bladder carcinoma (GBC), results from anatomical obstruction or motor abnormalities. We studied patients with GBC for antroduodenal motor dysfunction using manometry. METHODS: Forty-one patients with GBC without endoscopic gastric outlet obstruction and 10 healthy controls were evaluated using a symptom scoring system for gastric stasis, saline load test and water perfusion antroduodenal manometry. Fasting, post-prandial and post-octreotide motility were recorded and analysed on a computer using GiPC manometry software. RESULTS: Sixteen of 41 patients (39%) with GBC reported recurrent vomiting; patients with vomiting had a higher symptom score (13 [11-17] v. 6 [4-10], p<0.0001] and higher volume of aspirate on the saline load test (460 ml [210-650] v. 160 ml [70-260], p<0.0001) as compared with those without vomiting. Healthy subjects more often had spontaneous fasting migratory motor complex than patients with GBC (9/10 v. 13/41, p=0.002). The amplitudes of contractions in the antrum and duodenum were significantly lower in patients with GBC than in healthy subjects. Patients with GBC had lower fasting (157 [68-284] v. 190.5 [150-284], p=0.01) and post-prandial (200 [96-395] v. 284 [178-395], p<0.0001) antral motor indices than healthy subjects. Patients with GBC and vomiting had significantly lower contraction amplitude and motility indices than those without vomiting. Motility indices correlated inversely with the symptom score and volume of aspirate on the saline load test (Spearman correlation, p = 0.01 for all). CONCLUSION: Antroduodenal motor abnormalities are common in patients with GBC. These may explain the symptoms of gastric stasis and abnormal results of the saline load test in the absence of anatomical obstruction in such patients.

Structures and mechanisms of Nudix hydrolases.

Nudix hydrolases catalyze the hydrolysis of nucleoside diphosphates linked to other moieties, X, and contain the sequence motif or Nudix box, GX(5)EX(7)REUXEEXGU. The mechanisms of Nudix hydrolases are highly diverse in the position on the substrate at which nucleophilic substitution occurs, and in the number of required divalent cations. While most proceed by associative nucleophilic substitutions by water at specific internal phosphorus atoms of a diphosphate or polyphosphate chain, members of the GDP-mannose hydrolase sub-family catalyze dissociative nucleophilic substitutions, by water, at carbon. The site of substitution is likely determined by the positions of the general base and the entering water. The rate accelerations or catalytic powers of Nudix hydrolases range from 10(9)- to 10(12)-fold. The reactions are accelerated 10(3)-10(5)-fold by general base catalysis by a glutamate residue within, or beyond the Nudix box, or by a histidine beyond the Nudix box. Lewis acid catalysis, which contributes 10(3)-10(5)-fold to the rate acceleration, is provided by one, two, or three divalent cations. One divalent cation is coordinated by two or three conserved residues of the Nudix box, the initial glycine and one or two glutamate residues, together with a remote glutamate or glutamine ligand from beyond the Nudix box. Some Nudix enzymes require one (MutT) or two additional divalent cations (Ap(4)AP), to neutralize the charge of the polyphosphate chain, to help orient the attacking hydroxide or oxide nucleophile, and/or to facilitate the departure of the anionic leaving group. Additional catalysis (10-10(3)-fold) is provided by the cationic side chains of lysine and arginine residues and by H-bond donation by tyrosine residues, to orient the general base, or to promote the departure of the leaving group. The overall rate accelerations can be explained by both independent and cooperative effects of these catalytic components.

Long-term follow-up after pneumatic dilation for achalasia cardia: factors associated with treatment failure and recurrence.

BACKGROUND: Though most patients with achalasia cardia (AC) respond to pneumatic dilation (PD), one-third experienced recurrence. Long-term follow-up studies on factors associated with various outcomes are scanty. METHODS: In this retrospective study, 126 patients (36.5 +/- 14.6 yr, 76 male) with AC (diagnosed by esophagoscopy, barium esophagogram, and/or manometry) were followed up in person or through mail. The median dysphagia-free duration was calculated by Kaplan-Meier analysis. Factors associated with nonresponse and recurrence after PD were determined using univariate and multivariate analyses. RESULTS: Symptoms were dysphagia (126, 100%), chest pain (21, 17%), regurgitation (61, 48%), weight loss (33, 26%), and pulmonary symptoms (23, 18%); 5 of 126 (4%) had megaesophagus (> or =7 cm). The mean lower esophageal sphincter (LES) pressure was 38.7 +/- 16.8 mmHg. One hundred and fifteen of 126 (91%) patients responded to PD (90 (71%) to first session); 25 of these had recurrence of dysphagia after 15 +/- 17 months. Post-PD chest pain requiring hospitalization occurred in 21 of 126 (17%; one had an esophageal perforation). Post-PD LES pressure, which was assessed in 48 of 126 patients, had decreased by >50% from baseline in 14 of 29 responders, 0 of 11 nonresponders (p= 0.004, chi(2) test), and 5 of 8 relapsers. The median dysphagia-free duration by Kaplan-Meier analysis was 60 months (SE 2.7, 95% CI 54.7-65.3). On univariate analysis, male gender, pulmonary symptoms (nocturnal coughing spell, history of respiratory infection), absence of chest pain, and failure to achieve a reduction in LES pressure >50% after PD were associated with poor outcome; whereas age, grade of dysphagia, regurgitation, megaesophagus, and LES pressure before PD were not. Male gender was associated with poor outcome by multivariate-analysis. CONCLUSIONS: PD is an effective and safe treatment for AC. Post-PD LES pressure measurement may be helpful in assessing response. Male patients have poorer outcomes following PD.

Correlation of esophageal pH and motor abnormalities with endoscopic severity of reflux esophagitis.

Motility abnormalities, common in gastroesophageal reflux disease, are likely to be related to endoscopic esophagitis. We studied pH and manometry parameters in relation to the severity of esophagitis. Forty-seven patients with symptomatic gastroesophageal reflux disease for > 3 months were evaluated by: (i) endoscopy (grading of esophagitis by Savary-Miller classification); (ii) mucosal biopsy; (iii) manometry; and (iv) 24-h pH-metry. We found Savary-Miller's grades of: 0 (9 patients out of 47), I (16/47), II (16/47), III (4/47), IV (2/47). Distal esophageal contraction amplitude was lower in severe (grade II to IV) as compared with mild (grade 0 and I) esophagitis (49 [7-182] versus 83 [27-196] mmHg [P = 0.001]). The length and pressure in the lower esophageal sphincter (LES), duration and velocity of contraction in the body, number of episodes of reflux and long-duration reflux, longest reflux, median pH, per cent of time with pH < 4 and DeMeester scores were not significantly different between the two groups. The area under pH 4 showed a negative correlation with LES pressure and amplitude of distal esophageal contractions. We conclude that higher endoscopic grades of esophagitis are associated with lower amplitude of contraction in distal esophagus. Lower LES pressure and distal esophageal contraction amplitude are associated with greater area under curve for pH below 4.

Synthesis and anticonvulsant and neurotoxicity evaluation of N4-phthalimido phenyl (thio) semicarbazides.

The phenyl (thio) semicarbazide derivatives of phthalimido pharmacophore were synthesized and evaluated for their anticonvulsant and neurotoxic properties. Initial anticonvulsant screening was performed using intraperitoneal (i.p.), maximal electroshock-induced seizure (MES), subcutaneous pentylenetetrazole (scPTZ) and subcutaneous strychnine (sc STY)-induced seizure threshold tests in mice. Compound 2c afforded protection in all the three screens. Compounds except 1d, 2a and 2d showed no neurotoxicity up to 300 mg/kg. Compounds 1a, 1b, 2c, 2d, 2g and 2i were found to show oral MES activity. The compounds exhibited CNS depression and behavioral despair side effects, lesser than the conventional antiepileptic drugs.

Minimal hepatic encephalopathy: natural history, impact on daily functioning, and role of treatment.

Cirrhosis of liver is often complicated by minimal hepatic encephalopathy (mHE), which is detected by neuropsychiatric and neurophysiological tests. mHE develops more commonly in cirrhotics with severe liver disease and in those with esophageal and gastric varices. On follow up, these patients more often develop overt encephalopathy as compared to cirrhotics without mHE. mHE may affect daily activities like sleep, driving ability, alertness, social interaction, and communication. It is probably also an independent predictor of survival. The most practical treatment strategy for mHE has not been established; however, it can be treated as effectively as overt encephalopathy with similar agents. Treatment improves mHE in terms of psychometric tests, but improvement in daily functioning has not been well documented.

Tracheal lymphoepithelioma-like carcinoma: a case report.

Lymphoepithelioma like carcinoma is rare in locations other than nasopharynx. We report the second case of this tumour in trachea, in a young female patient, who was managed with concomitent surgery, radiotherapy and chemotherapy. The patient is disease free in the one-year follow up. The tumour presented difficulties during intubation for general anaesthesia and during surgery. Association with Epstein-Barr virus was not found in our case.

Autoimmune liver disease in children.

BACKGROUND AND AIM: Autoimmune liver disease (AILD) in children progresses to cirrhosis and liver failure if not diagnosed and managed in time. We prospectively analyzed our patients with liver disease for autoimmune etiology and their outcome with treatment. METHODS: All patients with liver disease were evaluated with liver function tests, abdominal ultrasonography, endoscopy, liver biopsy, viral markers and investigations for Wilson's disease. Immunoglobin (Ig)M hepatitis A virus, hepatitis E virus (HEV) and IgM hepatitis B core antibody were tested if acute viral hepatitis was suspected. Antinuclear antibody (ANA), antismooth muscle antibody (SMA), and liver kidney microsomal antibody (anti-LKM-1) were done in all cases. Autoimmune liver disease was diagnosed when one or more autoantibodies tested positive (> 1:40), and no other etiology of liver disease was identified. We also applied criteria proposed by the International Autoimmune Hepatitis Group. Cases diagnosed to have AILD were treated with immunosuppressive drugs. RESULTS: Autoimmune liver disease constituted 3.9% (6/153; median age and duration of illness 8.5 years and 3 months, respectively) of chronic liver disease cases. Four patients had acute hepatitis-like presentation. Of the six cases, two each were ANA and SMA +; one was anti-LKM-1 +, and the other was positive for both SMA and anti-LKM-1. Three of the patients achieved remission with combination therapy of oral prednisolone (OP) and azathioprine (AZT), and one with only OP. The other two patients were not treated. Two of the patients in remission have been weaned off from immunosuppressive therapy, and one is in a withdrawal phase. Another patient, while in biochemical remission developed superimposed anicteric acute HEV infection. CONCLUSION: Although AILD is uncommon in children, its search is rewarding, as remission is achieved with immunosuppressive therapy. Superimposed acute viral hepatitis can occur in endemic areas.

Prevalence and natural history of subclinical hepatic encephalopathy in cirrhosis.

BACKGROUND AND AIMS: The natural history of subclinical hepatic encephalopathy (SHE) is unknown. The present study was conducted to study the prevalence and the natural history of SHE in patients with cirrhosis of the liver. METHODS: One hundred and sixty-five patients with cirrhosis of the liver were studied. A total of nine psychometric tests (trail making and Wechsler adult intelligence scale-performance (WAIS-P) tests) were administered. Subclinical hepatic encephalopathy was present if two or more psychometric tests were abnormal. Seventy-two patients (SHE 40, without SHE 32) also underwent serial psychometric testing on follow-up visits at 6-8 week intervals. RESULTS: Subclinical hepatic encephalopathy was present in 103 (62.4%) patients. The number and figure connection, block design and picture completion tests were the most useful in the detection of SHE. Severity of SHE, as assessed by the number of abnormal tests, was greater in patients with more severe liver disease. During follow up, SHE tended to persist or worsen in patients with poorer liver function. Although other clinical complications were similar in different groups, overt hepatic encephalopathy developed more commonly in those patients who had SHE at entry compared to those who did not (22.6 vs 5.6%, P = 0.044). Among the patients with SHE, the development of overt hepatic encephalopathy was more common in patients with Child's score of > 6 than with Child's score of

Secretory production of Arthrobacter levan fructotransferase from recombinant Escherichia coli.

Levan fructotransferase (LFTase) from Arthrobacter ureafaciens K2032 was expressed with N-terminal fusion of a LacZ-derived secretion motif (TMITNSSSVP) using the lac promoter system in recombinant Escherichia coli JM109 [pUDF-A81]. In flask cultures, recombinant enzyme activity was detected in culture media, and sequence analysis of N-terminal residues showed that about 40% of the extracellular recombinant LFTase had an authentic N-terminus. In a fed-batch bioreactor containing recombinant E. coli at high cell concentrations (OD(600)>200), the extracellular LFTase accumulated to 46000 U ml(-1) (approximately 2.0 g l(-1)) which was almost 40% of total (intra- and extracellular) recombinant LFTase. The synthesized recombinant enzyme was secreted soon after gene expression was induced by IPTG. Prolonged high secretion caused cell lysis and growth inhibition during the production phase in fed-batch cultures. When lactose was added by continuous feed mode, the secretion of recombinant LFTase and hence the cell lysis were significantly delayed in spite of the increased synthesis level. Therefore the induced cell culture of recombinant E. coli could grow up to a much higher cell concentration with continuing recombinant enzyme synthesis. In the case of the controlled feed of lactose, the maximum activities (U ml(-1)) of total and extracellular LFTase were nearly 100% and 70% higher, respectively.

Role of Helicobacter pylori infection in hyperammonemia and subclinical hepatic encephalopathy in cirrhosis of liver.

INTRODUCTION: Gastric Helicobacter pylori infection is believed to be associated with a higher risk of hepatic encephalopathy among patients with cirrhosis of liver. However, the role of this infection in causation of subclinical hepatic encephalopathy has not been studied in detail. METHODS: Patients with cirrhosis of liver but no hepatic encephalopathy underwent venous blood ammonia measurement, psychometric tests (number connection tests [NCT] and figure connection tests [FCT]), and gastric biopsies for presence of H. pylori infection. The results of blood ammonia and psychometric tests in the H. pylori-positive and -negative study subjects were compared. RESULTS: Of 58 patients with liver cirrhosis studied, 31 had evidence of gastric H. pylori infection. Venous blood ammonia levels were comparable in patients with (median 29 mmol/L; range 18-47) and without (34 [15-48] mmol/L; p=ns) H. pylori infection. The time taken to complete NCT trail A (median 37 s [range 25-69] versus 36.5 [26-62]), NCT trail B (64 s [48-91] versus 63.5 [42-88]), FCT trail A (59 s [31-115] versus 58 [38-590]) and FCT trail B (76 s [55-187] versus 82 [36-125]) were similar in those with and those without H. pylori infection. For each of the four tests, the proportion of subjects with abnormal test results was similar among H. pylori-positive and -negative subjects. CONCLUSION: Presence of H. pylori infection among patients with cirrhosis of liver but no overt hepatic encephalopathy is not associated with increase in blood ammonia concentration or deterioration in psychomotor function.